In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF-308G>A (rs1800629), lymphotoxin-a (LTA) 252A>G (rs909253), IL10-3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF-308A carriers (NHL: per-allele odds ratio (ORallelic)=1.10, Ptrend=0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic=1.23, Ptrend=0.004). In the combined population, odds ratios were increased for TNF-308A carriers (NHL: ORallelic=1.13, Ptrend=0.0001; DLBCL: ORallelic=1.25, Ptrend=3.7 × 10-6; marginal zone lymphoma: ORallelic=1.35, Ptrend=0.004) and LTA 252G carriers (DLBCL: ORallelic=1.12, Ptrend = 0.006; mycosis fungoides: ORallelic=1.44, Ptrend=0.015). The LTA 252A>G/TNF-308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P=2.9 × 10 -8). Results suggested associations between IL10-3575T>A and DLBCL (Ptrend=0.02) and IL10-1082A>G and mantle cell lymphoma (Ptrend=0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF-308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.
Tumor necrosis factor (TNF) and lymphotoxin-a (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium / Skibola, C.F.; Bracci, P.M.; Nieters, A.; Brooks-Wilson, A.; De Sanjosé, S.; Hughes, A.M.; Cerhan, J.R.; Skibola, D.R.; Purdue, M.; Kane, E.; Lan, Q.; Foretova, L.; Schenk, M.; Spinelli, J.J.; Slager, S.L.; De Roos, A.J.; Smith, M.T.; Roman, E.; Cozen, W.; Boffetta, P.; Kricker, A.; Zheng, T.; Lightfoot, T.; Cocco, P.; Benavente, Y.; Zhang, Y.; Hartge, P.; Linet, M.S.; Becker, N.; Brennan, P.; Zhang, L.; Armstrong, B.; Smith, A.; Shiao, R.; Novak, A.J.; Maynadie, M.; Chanock, S.J.; Staines, A.; Holford, T.R.; Holly, E.A.; Rothman, N.; Wang, S.S.. - In: AMERICAN JOURNAL OF EPIDEMIOLOGY. - ISSN 0002-9262. - STAMPA. - 171:3(2010), pp. 267-276. [10.1093/aje/kwp383]
Tumor necrosis factor (TNF) and lymphotoxin-a (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium
Roman, E.;Boffetta, P.;Smith, A.;
2010
Abstract
In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF-308G>A (rs1800629), lymphotoxin-a (LTA) 252A>G (rs909253), IL10-3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF-308A carriers (NHL: per-allele odds ratio (ORallelic)=1.10, Ptrend=0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic=1.23, Ptrend=0.004). In the combined population, odds ratios were increased for TNF-308A carriers (NHL: ORallelic=1.13, Ptrend=0.0001; DLBCL: ORallelic=1.25, Ptrend=3.7 × 10-6; marginal zone lymphoma: ORallelic=1.35, Ptrend=0.004) and LTA 252G carriers (DLBCL: ORallelic=1.12, Ptrend = 0.006; mycosis fungoides: ORallelic=1.44, Ptrend=0.015). The LTA 252A>G/TNF-308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P=2.9 × 10 -8). Results suggested associations between IL10-3575T>A and DLBCL (Ptrend=0.02) and IL10-1082A>G and mantle cell lymphoma (Ptrend=0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF-308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
